NEW ASPECTS ON ETIOLOGY, BIOCHEMISTRY, AND THERAPY OF PORTAL-SYSTEMICENCEPHALOPATHY - A CRITICAL SURVEY

There is scientific agreement that portal systemic encephalapathy (PSE ) is caused morphologically by portal systemic shunts and biochemicall y by constituents of the portal venous blood; Ammonium has a key role in the pathogenesis of PSE. Direct correlations with the degree of PSE have been established exclusively with glutamine, i.e. the terminal p roduct of the peripheral detoxification of ammonium. In PSE, ammonium is probably responsible for damage to astrocytic ; and neuronal cells. Ammonium's toxic effect is due to the intracerebral glutamine synthes is. After several metabolic steps, which will be discussed in detail, brain cell damage is caused directly of indirectly (exitotoxically) by energy deficiency. Hyperammonemia and PSE are each well defined thoug h different forms of disturbance. Therefore, ammonium is not the sole decisive factor in the pathogenesis of PSE. We performed a detailed an d critical analysis of all studies on amino acid therapy of PSE, espec ially those that were randomized and controlled. This analysis reveale d a close and direct correlation between qualitative and quantitative dosages of amino acids on one hand, and parallel improvements of amino acid imbalance (essentially associated with PSE) and degree of PSE on the other. A close and direct dose/efficacy correlation must be assum ed. Disturbed plasmatic amino acid homeostasis and cerebral monoaminer gic neurotransmission are probably important pathogenic factors of PSE . A fundamental cofactor in the efficacy of each adequate amino acid t herapy might be a substantial decrease of endogenous ammonium producti on. Physiologic benzodiazepines may also have an important function in the pathogenesis of PSE: not so, however, the glutamate-ergic and GAB A-ergic neurotransmission,which are disturbed principally in PSE. In c lose correlation to pathogenesis, established and proposed therapies o f PSE are critically discussed. (C)Elsevier Science Inc. 1997.